tbuckley/cabot-search huggingface dataset:
Real-life data of antiandrogens (AA) use in metastatic androgen receptor positive triple negative breast cancer (AR+ TNBC): The ATOVAT retrospective French cohort.
Authors: Yasmine Rhanine, Herve R. Bonnefoi, Anthony Goncalves, Marc Debled, Sylvestre Le Moulec, Nathalie Bonichon-Lamichhane, Benedicte Dubroca-Dehez, Thomas Grellety
Journal: Journal of Clinical Oncology (2022)

e13074 Background: AR+ TNBC account for around 25% of all TNBC. Identification of those patients is difficult since AR expression (IHC) testing is not routinely recommended. Published data of 3 trials using different antiandrogens (AA) found clinical benefit rates (CBR) at 6 months ranging from 19 to 29% with excellent toxicity profiles. The aim of this retrospective trial was to assess the clinical benefit of AA in real life. Methods: Patients with metastatic AR+ (IHC staining &gt; 10% assessed by local laboratories) TNBC treated with an antiandrogen in metastatic setting were eligible. Patients should have received at least one dose of the following AA: abiraterone acetate, enzalutamide or bicalutamide. Antiandrogens had to be given after documented progression and must not be carried out as part of a clinical trial. Patients could be chemotherapy naïve for their metastatic disease or have received any number of previous line. 30 oncology centers involved in clinical research in France were screened by questionnaire and data were collected in each patient files. The aim was to describe the 6-months CBR and safety in real-life patients. Assessable patients received at least 4 weeks of AA and present at least one disease assessment. Results: 26 patients from 5 French sites were deemed eligible and 24 patients were assessable. Treatment were conducted between January 2002 and January 2021. Median age at initiation of AA was 70 years (range 50-90). 50 % (N = 13) presented liver and/or lung mets and 27% (N = 7) non progressing and non-symptomatic cerebral mets. Median number of previous line of chemotherapy was 3 (range 0-10). AA used were: abiraterone acetate (62%), enzalutamide (8%) and bicalutamide (30%). Median time from mets diagnosis to AA treatment initiation was 18 months (range 0-168). 6-months CBR were 29% (N = 7) with 5 objective responses (2 CR, 3 PR) and 2 SD. 4-months CBR were 33% (N = 8). PFS and OS were 3.2 months (0.8- 36.1) and 9.5 (1.3-63.8) months, respectively. 2 pts further received second line AA with 1 with SD as a best response. 57% (4/7) of patients presenting 6-months clinical benefit received AA in first line versus 18% (3/17).There were no grade 3 or more side effects reported. Conclusions: Real-life data of antiandrogens use in metastatic AR+ TNBC are in line with data from published clinical trials using the same drugs. There were no new safety signal in this retrospective cohort supporting the use of antiandrogens in AR+ (&gt; 10%) TNBC in the absence of other therapeutic opportunity or available clinical trials.
Unmet psycho-social needs of parents of children who die from cancer.
Authors: Isabel Josephs, Jennifer JG Welch, Margaret Mannix
Journal: Journal of Clinical Oncology (2022)

e24005 Background: Cancer is the leading disease-related cause of death for children in the United States, but there is limited data on the needs of caregivers who have lost a child to cancer, and few evidence-based bereavement interventions exist. Parents whose children die from cancer have increased rates of depression, anxiety, and health problems. Prior studies have shown that bereaved parents desire continued contact with their child’s medical team and to connect with parents who have had similar losses. Methods: This is a cross sectional survey of primary caregivers of pediatric patients who died from cancer and were cared for at a moderate size pediatric oncology program (50 new diagnoses per year) from 2010 to 2020. Participation was solicited by mail in English and Spanish. Research packets contained five surveys: Demographic Survey, The Needs Assessment for Family Caregivers Bereaved to Cancer, Quality of Life Survey (SF-36), Brief Grief Assessment, and Social Support Questionnaire (SSQ-6). Interested subjects also participated in a semi-structured, in-depth qualitative interview. Results: One hundred six potentially eligible families were identified. 27 families consented, 10 were without a known address, and 2 opted out. Twenty research packets and 9 interviews were completed, representing 19% of the population of interest and 23% of the invited population. The sample was diverse in gender, age, income, and education level, but not race. The greatest unmet needs were finding meaning in the death, personal wellness, and social activities. Caregivers reported good physical functioning but poor emotional well-being and fatigue. Complicated grief was most profound in the interference (grief interfering with life) and intrusion (images and thoughts of the child) domains. Quantity of social support correlated with satisfaction with social support (P = 0.02). Bereaved parents with greater unmet needs were found to have poorer quality of life in the following domains: energy/fatigue (P = 0.005), role limitations due to emotional problems (P = 0.01), pain (P = 0.01), and emotional well-being (P = 0.02). Greater unmet needs did not correlate to more complicated grief (P = 0.30) or satisfaction with social support (P = 0.08). Interview themes elicited were inadequate current bereavement services, necessary support for siblings, desired contact with the medical team, and connections to other bereaved caregivers. Conclusions: Findings support the need for implementation of more intensive evidence-based bereavement programs for families of children who died from cancer. The data suggests that interventions targeting emotional well-being and increased social supports, in the form of connections to the medical team and other bereaved families, will be the most efficacious in mitigating poor bereavement-related outcomes.
MRI-guided transurethral ultrasound ablation for localized clinically significant prostate cancer: 12-month clinical outcomes of a phase 2 study
Authors: E.H.M. Yli-Pietilä, M. Anttinen, P. Mäkelä, A. Viitala, P. Nurminen, O. Ettala, P. Taimen, R. Blanco Sequeiros, P.J. Boström
Journal: European Urology (2022)
Detection of clinically significant prostate cancer in mpMRI visible lesions: Size matters. Results from a large, two-institutional series
Authors: A. Stabile, G. Gandaglia, E. Mazzone, F. Barletta, D. Robesti, G.O. Cirulli, D. Cannoletta, F. Pellegrino, L. Nocera, G. Sorce, M. De Angelis, C. Bravi, V. Cucchiara, A. Martini, N. Fossati, F. De Cobelli, A. Esposito, G. Brembilla, T. Seisen, M. Roupret, R.J. Karnes, F. Montorsi
Journal: European Urology (2022)
5 years follow-up outcomes of pelvic floor rehabilitation protocol in subjects with lifelong premature ejaculation: The definitive long-term evaluation
Authors: A.L. Pastore, A. Fuschi, Y. Al Salhi, L. Capone, A. Martoccia, P.P. Suraci, S. Scalzo, G. Bozzini, S. Maruccia, E. Illiano, A. Zucchi, E. Costantini, A. Carbone
Journal: European Urology (2022)
Considerations for Generic-to-Generic Levothyroxine Switching
Authors: James V. Hennessey
Journal: JAMA Internal Medicine (2022)

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Are we providing adequate information? patient-specific clinical trial information at NCI-designated cancer center websites.
Authors: Ana I. Velazquez Manana, Dame Idossa, Kelly Jasmin Meza, Juan J. Rodriguez Vargas, Narjust Duma
Journal: Journal of Clinical Oncology (2022)

e18602 Background: Disparities persist in the recruitment and enrollment of diverse populations to cancer clinical trials (CT). Barriers to CT participation are numerous and include structural inequities that limit access, stringent eligibility criteria, financial barriers, provider bias, and patient knowledge. While national societies recommend patient educational materials should be written ≤6th grade reading level, most CT online information available is complex. We evaluated the accessibility, readability, and content of patient-specific CT information from NCI-designated cancer center websites (CCW). Methods: We conducted a qualitative review of CT information in 64 clinical NCI CCW. We reviewed each CCW’s patient-specific CT information to evaluate content, reading level, and navigation. Readability was evaluated using validated measures [i.e., Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), Coleman-Liau Index (CLI), and Simple Measure of Gobbledygook (SMOG) Grade Level] and an average readability score. Data was summarized using descriptive statistics. Results: Most CCW made CT information easily accessible, 62 had a CT-specific website of which 61% required only 1-click from the homepage and 5% required ≥3 clicks. Common patient-specific information included definition of CT (89%), CT phases (66%), guidance on how to decide if you should enroll in a CT (59%), risks and benefits of participation (53%), informed consent (48%), and financial considerations (30%). Only 16% of CCW contained CT information for patients with limited or no English proficiency (14% Spanish, 8% Chinese). CT educational content required a reading level of ≥10 th grade (Table). 44% of websites included links to outside educational resources, such as the NCI. None of the websites included CT-specific supportive resources (i.e., transportation, navigation, financial assistance, etc.). Most CCW included a CT search bar (77%), yet when searching for a specific cancer type (i.e., breast cancer) 53% yielded a top search result that was disease agnostic or for a different cancer type. 72% included CT descriptions, 58% their eligibility criteria, and 29% included pre-screening forms or links to CT-specific inquiries. Conclusions: Most NCI designated CCW contain CT information at a high literacy level with suboptimal search options and very limited resources/information in other languages. Our findings highlight missed opportunities to develop and advertise CT-specific supportive services and to disseminate CT education materials that meet the literacy and language needs of the increasingly diverse US population.[Table: see text]
Impact of neighborhood disadvantage on biological and clinical indicators of anxiety among newly diagnosed patients with breast cancer.
Authors: Neha Goel, Molly Ream, Michael Antoni
Journal: Journal of Clinical Oncology (2022)

568 Background: Women living in disadvantaged neighborhoods consistently having worse breast cancer (BC) survival. Recent studies have identified that disparities by neighborhood disadvantage persist after controlling for patient, tumor, and National Comprehensive Cancer Network-guideline concordant treatment. This persistent disparity suggests unaccounted mechanisms by which neighborhood disadvantage “gets under the skin” to impact to shorter BC survival. Methods: Women with stage 0-3 BC between 1998-2005 were enrolled in a clinical trial for stress management 2-10 weeks post-surgery and before initiating adjuvant treatment. At baseline, women provided an evening-time serum cortisol sample and were administered a structured clinical interview of anxiety symptoms (Hamilton Anxiety Rating Scale; HAM-A). Of the 240 women who enrolled in the study and completed baseline procedures, home addresses were provided by 225 women (93.8%). The addresses were used to determine the Area Deprivation Index (ADI), a validated measure of neighborhood disadvantage, using the University of Wisconsin Neighborhood Atlas. Women were categorized as low (1-3) versus high (4-10) ADI. Linear regression analyses was used to assess the relationship between ADI and serum cortisol and logistic regression to assess whether ADI group predicted the presence of clinically significant anxiety per the HAM-A. Results: The average age of our population was 50.4 years old (range 23-70 years) and the majority were non-Hispanic White (63.6%). Most patients had stage 1 (37.8%) or 2 (38.2%) disease. The majority lived in advantaged neighborhoods (low ADI, 77.8%). On the HAM-A, 46.8% of women reported clinically significant anxiety symptoms. When controlling for age, stage, and type of surgery, women with a high ADI had higher cortisol levels than women in with a low ADI (Beta =.19, t(117) = 2.18, p=.031). Moreover, accounting for age, stage, and type of surgery, women with a high ADI were nearly two times as likely to have clinically significant anxiety symptoms in the HAM-A clinical interview (OR 1.99, 95%CI 1.01, 3.90, p =.046). Conclusions: This study identified that neighborhood disadvantage is significantly associated with higher levels of cortisol and clinical anxiety. Future studies need to evaluate stress pathways as a potential mechanism by which neighborhood disadvantage "gets under the skin" to impact BC-specific survival.
An Immune-metabolic signature (IMMETCOLS) identifies three clusters in mCRC with different immune-phenotype distribution and potential clinical implications.
Authors: Ivan Archilla, Leire Pedrosa, Marta Garcia de Herreros, Laia Fernandez-Mañas, Francis Esposito, Pedro Jares, Carolina Figueras, Sandra López, Helena Oliveres, Carles Foguet, Marta Cascante, Joan Maurel, Miriam Cuatrecasas
Journal: Journal of Clinical Oncology (2022)

e15534 Background: The overall response rate following immune check-point blockade (ICB) is &lt; 5% in microsatellite stable (MSS) advanced colorectal cancer (mCRC), and between 30-35% in MSI mCRC. We here evaluate the relationship between our immune-metabolic signature (IMMETCOLS) distribution (cluster (IMC) 1; mesenchymal glycolytic, IMC 2; epithelial-non glycolytic and IMC 3; epithelial mitochondrial oxidative) with immune phenotypes (inflamed (IF), immune-excluded (IE) and immune-desert (ID)) in MSS and MSI mCRC patients (pts). Methods: We have analyzed IMMETCOLS in a retrospective cohort of 128 mCRC pts enriched with MSI-H and BRAF genotype using the nCounter platform (Nanostring Technologies, US). Immune phenotypes were evaluated by immunohistochemistry using 7 immune markers (CD68, CD163, CD8, CD3, FOXP3, PD-L1 and PD1) in a subset of 47 mCRC pts (27 MSS and 20 MSI), in TMAs containing 4 cores from the center of the tumor (CT) and invasive front (IF). The number of stained immune cells was counted using a computerized image analysis system, and PD-L1 was evaluated using CPS score (&lt; 1 vs &gt; 1). Patients having a CD3 cell count below 572 cells/mm2 and a CD8 density below 175 cells/mm2 in IF or CT were considered as ID. (Halama Nils, 2011). CD3 density was also semi-quantitatively estimated in peritumoral stroma and intra-tumoral (range 1-4), defining as IE those cases with a difference &gt; 1 between the two regions in both IF and CT (Brooks JM, 2019). Results: Cluster distribution was similar between MSI (IMC1-40%, IMC2-20% and IMC-40%) and MSS (IMC1-34%, IMC2-24%, IMC3-43%) pts. Patients with high LDH levels (&gt; 1.5ULN) were enriched with IMC3 phenotype (p &lt; 0.0001). MSI have increased CD3 (p = 0.002), CD68 (p = 0.002) and CD163 (p = 0.001) in CT than MSS patients. IMC1 pts had increased CD163/CD68 ratio in CT (p = 0.004). 75% of MSI pts were IE and 25% IF. 55% of MSS pts were IE, 38% ID and 7% IF. IMMETCOLS/ immune-phenotype distribution was: IMC1 (16% ID/ 84% IE), IMC2 (12% ID/ 63% IE/ 25% IF) and IMC3 (35%ID/ 47% IE/ 18% IF). PD1 immuno-expression &gt; 1% (IF and CT) and PD-L1 positivity was observed in 38%, 30% and 28% of pts respectively. There were no differences in PD-L1 (CPS) and PD1 expression between MSS and MSI tumors. Inflamed tumors show higher PD-L1 expression compared with IE and ID immune-phenotypes (p = 0.014). PD1 &gt; 1% expression at IF was significatively lower in IMC1 vs IMC2 and IMC3 tumors (p = 0.032). Conclusions: IMC1 subtype is associated with low PD1 expression, high CD163/CD68 ratio and IE phenotype even in MSI-H mCRC patients. Therefore, IMMETCOLS testing would be of value to identify MSI mCRC pts that do not benefit to ICB therapy.
HGG-19. Co-occurrences of a high-grade glioma with cavernous malformations and pathogenic variants in<i>PDCD10</i> and<i>SMARCA4</i>
Authors: Hannah Glanz, Sudarshawn Damodharan, Kelcy Smith-Simmer, Kristin Bradley, Susan Rebsamen, Kristin Casey, Bermans Iskandar, Jeffrey Helgager, Diane Puccetti
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: The co-occurrence of multiple disease processes can make for more challenging diagnoses. Here we report an unusual case of a patient found to have an IDH1-mutant high-grade glioma along with multiple cerebral cavernous malformations and pathogenic germline variants in PDCD10 and SMARCA4. CASE DESCRIPTION: A 17-year-old female presented with left arm paresthesia and weakness along with persistent headaches within the frontal and occipital regions that progressed in intensity to include nausea and emesis. A fast sequence magnetic resonance imaging (MRI) of her head was obtained that revealed the presence of multiple bilateral cystic lesions suspicious for cavernomas, with the most notable lesion in the right parietal lobe. Ophthalmology consultation revealed grade III papilledema bilaterally. A full brain MRI with and without contrast was obtained and demonstrated a right anterior parietal lobe lesion with associated mass effect, as well as multiple bilateral supratentorial and left cerebellar cavernous malformations. The patient underwent tumor debulking of her dominant lesion. Pathology revealed an IDH1-mutant diffuse astrocytoma, WHO grade III. Tumor genetic testing was done and identified a SMARCA4 and two TP53 variants. Germline genetic testing was then pursued which revealed a PDCD10 pathogenic variant consistent with familial cerebral cavernous malformation syndrome and a likely pathogenic variant in SMARCA4. Treatment of her high-grade-glioma included radiation therapy followed by maintenance oral temozolomide. DISCUSSION: This case illustrates the unusual co-occurrences of a high-grade glioma with familial cavernous malformation syndrome and germline pathogenic variants in PDCD10 and SMARCA4. Our patient continues to do well clinically, but because of her risk of developing small cell carcinoma of the ovary she has elected to undergo a prophylactic bilateral salpingo-oophorectomy. Recognition of abnormal genetic results is critical in the setting of multiple disease processes and can play a crucial role in the on-going care for a patient.
Multicancer early detection with a spectroscopic liquid biopsy platform.
Authors: Matthew Baker, James Munro Cameron, Alexandra Sala, Georgios Antoniou, Holly Butler, Paul Brennan, Justin Conn, Siobhan Connal, Mark Hegarty, David Palmer, Benjamin Smith
Journal: Journal of Clinical Oncology (2022)

3034 Background: A rapid, low-cost, sensitive, multi-cancer early detection (MCED) test would be transformational in the diagnostics field. Earlier cancer detection and instigation of treatment can increase survival rates. An effective test must accurately identify the small proportion of patients with typically non-specific symptoms who actually have cancer. Such symptoms don’t easily segregate by organ system, necessitating a multi-cancer approach. Methods: In this large-scale study ( n = 2094 patients) we applied the Dxcover Cancer Liquid Biopsy to differentiate cancer against non-cancer, as well as organ specific tests to identify cancers of the brain, breast, colorectal, kidney, lung, ovary, pancreas, and prostate. The test uses Fourier transform infrared spectroscopy to analyze all macromolecules in a minute volume of patient serum, and machine learning to build a classifier of the resultant spectral profiles for calling the likelihood of cancer. Results: For the overall cancer classification, our model achieved 90% sensitivity with 61% specificity when tuned for sensitivity, with detection rates of 93% for stage I, 84% for stage II, 92% for stage III and 95% for stage IV. We also tuned for maximum sensitivity or specificity, whilst the other statistic was fixed above a minimum value of 45%. This resulted in 94% sensitivity with 47% specificity, and 94% specificity with 48% sensitivity, respectively. For organ specific cancer classifiers area under the curve values were calculated for all cancers: brain (0.90), breast (0.74), colorectal (0.91), kidney (0.91), lung (0.90), ovarian (0.85), pancreatic (0.81) and prostate (0.85). Conclusions: Cancer treatment is often more effective when given earlier and this low-cost strategy can facilitate the requisite earlier diagnosis. With further development, the Dxcover MCED test could have a significant impact on early detection of cancer, which is vital in the quest for improved survival and quality of life.
Prognostic impact of clear cell renal cell carcinoma molecular subtypes determined on formalin-fixed paraffin-embedded tissue samples on outcome after complete surgical metastasectomy
Authors: E. Roussel, L. Kinget, A. Verbiest, B. Boeckx, G. Couchy, S. Caruso, J. Zucman-Rossi, M. Baldewijns, S. Joniau, H. Van Poppel, D. Lambrechts, M. Albersen, B. Beuselinck
Journal: European Urology (2022)